ABSTRACT This is an application to establish the University of Michigan Proteogenomic Data Analysis Center (UM- PGDAC). The National Cancer Institute (NCI) has made significant investments in new technology platforms for cancer proteomics through the Clinical Proteomic Tumor Analysis Consortium (CPTAC) initiative. Proteomics provides complementary information not apparent from the analysis of genomic and transcriptomic data alone. First, it is critical to identify which of the thousands of novel or previously poorly characterized transcripts or sequence variants discovered using genomic and transcriptomic approaches are expressed at the protein level, prioritizing such variants for subsequent validation studies. Second, integration of quantitative information across multiple data types has emerged as a powerful strategy for reconstructing targetable pathways in cancer and for nomination of potential drug targets. At the same time, sophisticated, integrative analyses across genome and proteome data require advanced bioinformatics tools and stringent quality control measures. UM-PGDAC is uniquely positioned to implement advanced bioinformatics infrastructure to address these challenges and apply it across CPTAC data. It brings together a multi-disciplinary team of scientists who are leading experts in the areas of computational proteomics, transcriptomics, genomics, cancer systems biology and precision oncology. The team is anchored at the Michigan Center for Translational Pathology (MCTP), which has a long history of successful collaborations between the individual investigators. UM-PGDAC builds upon more than a decade of highly relevant work that resulted in the development of a comprehensive infrastructure required for proteogenomics and multi- omics data integration research. UM-PGDAC investigators will work to further improve the speed and accuracy of proteogenomics analyses. The integrated genome/transcriptome/proteome pipelines used by the UM-PDGAC will be enhanced with automated data visualization capabilities and report generation tools for presenting the findings to cancer biologists in a transparent and easy to interpret manner. UM-PGDAC will work collaboratively with other members of the CPTAC to ensure minimal duplication of efforts, efficient exchange of data and bioinformatics methods and tools and interoperability via the use of common file formats and data standards. Building upon its extensive experience in the area of biomarker discovery and precision oncology, further enhanced through participation of UM-PGDAC investigators in the EDRN, SPORE, and other NIH funded initiatives, UM-PGDAC will engage in a second round of prioritization work to select candidate cancer-specific proteins and peptides for subsequent targeted validation using multiplex proteomic assays. Finally, UM-PGDAC will take advantage of a unique opportunity ? in the form of the NCI funded T32 Proteome Informatics Training Program at the University of Michigan ? to create a unique environment for training the new generation of cancer researchers versed in proteomics technology.